To discover possible pathogenetic mechanisms of fiber degeneration, the three-dimensional pathology of the peripheral nervous system will be evaluated in inherited and acquired neuropathies of man utilizing nerve biopsy and necropsy tissue and morphometric evaluation of cytons of ventral horn and spinal ganglia and of nerve fibers in fasciculus gracilis, nerve roots and various levels of limb nerves. A controlled trial of predinsone vs no treatment is planned in patients with chronic inflammatory polyradiculoneuropathy. A systematic quantitative analysis of serum and tissue lipids and of lipid enzymes will be undertaken in various inherited and other neuropathies. Using quantitative measurement of cutaneous sensation, recording the compound action potential in vitro and morphometric evaluation of nerve, mechanisms of paresthesia and of painfulness will be evaluated. In experimental animals we will attempt to produce: distal axonal degeneration and axonal atrophy and segmental demyelination by x-irradiation of cyton or by local application of inhibitors of protein synthesis; demyelination and sclerosis of posterior column by limb amputation; and experimental uremic neuropathy by 5/6th nephrectomy and creatinine feeding or ion myoinositol feeding or ion methyl quanidine feeding. In lead neuropathy the blood nerve barrier and the interstitial pressure will be assessed. In experimental myasthenia gravis the pathologic alterations of peripheral nervous system will be investigated.